Abstract [en]

Fear memories can be attenuated by reactivation followed by disrupted reconsolidation. Using functional magnetic resonance imaging we recently showed that reactivation and reconsolidation of a conditioned fear memory trace in the basolateral amygdala predicts subsequent fear expression over two days, while reactivation followed by disrupted reconsolidation abolishes the memory trace and suppresses fear. In this follow-up study we demonstrate that the behavioral effect persists over 18 months reflected in superior reacquisition after undisrupted, as compared to disrupted reconsolidation, and that neural activity in the basolateral amygdala representing the initial fear memory predicts return of fear. We conclude that disrupting reconsolidation have long lasting behavioral effects and may permanently erase the fear component of an amygdala-dependent memory.

Björkstrand, Johannes

Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Psychology.

2017 (English)Doctoral thesis, comprehensive summary (Other academic)

Abstract [en]

The amygdala is crucially involved in the acquisition and retention of fear memories. Experimental research on fear conditioning has shown that memory retrieval shortly followed by pharmacological manipulations or extinction, thereby interfering with memory reconsolidation, decreases later fear expression. Fear memory reconsolidation depends on synaptic plasticity in the amygdala, which has been demonstrated in rodents using both pharmacological manipulations and retrieval-extinction procedures. The retrieval-extinction procedure decreases fear expression also in humans, but the underlying neural mechanism have not been studied. Interfering with reconsolidation is held to alter the original fear memory representation, resulting in long-term reductions in fear responses, and might therefore be used in the treatment of anxiety disorders, but few studies have directly investigated this question.

The aim of this thesis was to examine the effects of the retrieval-extinction procedure on amygdala activity and behavioral fear expression in humans. The work presented here also investigated whether findings from studies on recent fear memories, established through fear conditioning, extends to naturally occurring long-term phobic fears.

Study I, combining fear conditioning and a retrieval-extinction procedure with functional magnetic resonance imaging (fMRI), demonstrated that memory retrieval shortly followed by extinction reduces later amygdala activity and fear expression in healthy subjects. In Study II, these subjects were re-tested 18 months later. The results showed that the effects on fear expression were still present and that initial amygdala activity predicted long-term fear expression. Using an adapted version of the retrieval-extinction procedure, Study III showed that memory retrieval shortly followed by exposure to spider pictures, attenuates subsequent amygdala activity and increases approach behavior in subjects with life-long fear of spiders. In Study IV, these subjects were re-tested 6 months later, and the results showed that effects on amygdala activity as well as approach behavior were maintained.

In summation, retrieval-extinction leads to long-lasting reductions in amygdala activity and fear expression. These findings are consistent with the hypothesis that retrieval-extinction alters an amygdala dependent fear memory. Retrieval-extinction can also attenuate long-term phobic fears, indicating that this manipulation could be used to enhance exposure-based treatments for anxiety disorders.

Place, publisher, year, edition, pages

Uppsala: Acta Universitatis Upsaliensis, 2017. p. 72

Series

Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Social Sciences, ISSN 1652-9030 ; 140